Method and apparatus employing ultrasound energy to treat body sphincters

ABSTRACT

Methods and apparatus for treating gastroesophageal reflex and other luminal conditions provide for delivering acoustic energy to a body lumen to remodel tissue surrounding the body lumen. In the case of treating GERD, a catheter carrying an ultrasonic or other vibrational transducer is introduced to the lower esophageal sphincter, and acoustic energy is delivered to the sphincter in order to tighten or bulk the sphincter such that reflex is reduced.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 10/611,838 (Attorney Docket No. 41655-703.201), filed Jun. 30,2003, which is a non-provisional of U.S. patent application Ser. No.60/419,317 (Attorney Docket No. 41655-703.102), filed Oct. 16, 2002,which contained the entire content of prior Provisional Application No.60/393,339 (Attorney Docket No. 41655-703.101), filed on Jul. 1, 2002,with additional material added, the full disclosures of which areincorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

In a general sense, the invention is directed to systems and methods fortreating interior tissue regions of the body. More specifically, theinvention is directed to systems and methods for treating dysfunction inbody sphincters and adjoining tissue, e.g., in and around the loweresophageal sphincter and cardia of the stomach.

2. Description of the Background Art

The gastrointestinal (GI) tract extends from the mouth to the anus, andincludes the esophagus, stomach, small and large intestines, and rectum.Along the way, ring-like muscle fibers called sphincters control thepassage of food from one specialized portion of the GI tract to another.The GI tract is lined with a mucosal layer about 1-2 mm thick thatabsorbs and secretes substances involved in the digestion of food andprotects the body's own tissue from self-digestion. The esophagus is amuscular tube that extends from the pharynx through the esophagealhiatus of the diaphragm to the stomach. Peristalsis of the esophaguspropels food toward the stomach as well as clears any refluxed contentsof the stomach.

The junction of the esophagus with the stomach is controlled by thelower esophageal sphincter (LES), a thickened circular ring of smoothesophageal muscle. The LES straddles the squamocolumnar junction, orz-line--a transition in esophageal tissue structure that can beidentified endoscopically. At rest, the LES maintains a high-pressurezone between 10 and 30 mm Hg above intragastric pressures. The LESrelaxes before the esophagus contracts, and allows food to pass throughto the stomach. After food passes into the stomach, the LES constrictsto prevent the contents from regurgitating into the esophagus. Theresting tone of the LES is maintained by muscular and nerve mechanisms,as well as different reflex mechanisms, physiologic alterations, andingested substances. Transient LES relaxations may manifestindependently of swallowing. This relaxation is often associated withtransient gastroesophageal reflux in normal people. Muscularcontractions of the diaphragm around the esophageal hiatus duringbreathing serve as a diaphragmatic sphincter that offers secondaryaugmentation of lower esophageal sphincter pressure to prevent reflux.

The stomach stores, dissolves, and partially digests the contents of ameal, then delivers this partially digested food across the pyloricsphincter into the duodenum of the small intestine in amounts optimalfor maximal digestion and absorption. Feelings of satiety are influencedby the vagally modulated muscle tone of the stomach and duodenum as wellas through the reception and production of biochemicals (e.g., hormones)therein, particularly the gastric antrum.

Finally, after passage of undigested food into the large intestine, itis passed out of the body through the anal sphincter. Fluids unused bythe body are passed from the kidneys into the bladder, where a urinarysphincter controls their release.

A variety of diseases and ailments arise from the dysfunction of asphincter. Dysfunction of the lower esophageal sphincter, typicallymanifest through transient, relaxations, leads to reflux of stomachacids into the esophagus. One of the primary causes of the sphincterrelaxations is believed to be aberrant vagally-mediated nerve impulsesto the LES and cardia (upper part of the stomach). This condition,called Gastroesophageal Reflux Disease (GERD), creates discomfort suchas heartburn and with time can begin to erode the lining of theesophagus—a condition that can progress to esophagitis and apre-cancerous condition known as Barrett's Epithelium. Complications ofthe disease can progress to difficulty and pain in swallowing,stricture, perforation and bleeding, anemia, and weight loss.Dysfunction of the diaphragmatic sphincter, such as that caused by ahiatal hernia, can compound the problem of LES relaxations. It has beenestimated that approximately 7% of the adult population suffers fromGERD on a daily basis. The incidence of GERD increases markedly afterthe age of 40, and it is not uncommon for patients experiencing symptomsto wait years before seeking medical treatment.

Treatment of GERD includes drug therapy to reduce or block stomach acidsecretions, and/or increase LES pressure and peristaltic motility of theesophagus. Most patients respond to drug therapy, but it is palliativein that it does not cure the underlying cause of sphincter dysfunction,and thus requires lifelong dependence. Invasive abdominal surgicalintervention has been shown to be successful in improving sphinctercompetence. One procedure, called Nissen fundoplication, entailsinvasive, open abdominal surgery. The surgeon wraps the gastric fundisabout the lower esophagus, to, in effect, create a new “valve.” Lessinvasive laparoscopic techniques have also been successful in emulatingthe Nissen fundoplication. As with other highly invasive procedures,antireflux surgery is associated with the risk of complications such asbleeding and perforation. In addition, a significant proportion ofindividuals undergoing laparascopic fundoplication report difficultyswallowing (dysphagia), inability to vomit or belch, and abdominaldistention.

In response to the surgical risks and drug dependency of patients withGERD, new trans-oral endoscopic technologies are being evaluated toimprove or cure the disease. One approach is the endoscopic creation andsuturing of folds, or plications, in the esophageal or gastric tissue inproximity to the LES, as described by Swain, et al, [Abstract],Gastrointestinal Endoscopy, 1994; 40:AB35. Another approach, asdescribed in U.S. Pat. No. 6,238,335, is the delivery of biopolymerbulking agents into the muscle wall of the esophagus. U.S. Pat. No.6,112,123 describes RF energy delivery to the esophageal wall via aconductive medium. Also, as described in U.S. Pat. No. 6,056,744, RFenergy has been delivered to the esophageal wall via discretepenetrating needles. The result is shrinkage of the tissue andinterruption of vagal afferent pathways some believe to play a role inthe transient relaxations of the LES.

The above endoscopic techniques all require the penetration of theesophageal wall with a needle-like device, which entails the additionalrisks of perforation or bleeding at the puncture sites. Special care andtraining by the physician is required to avoid patient injury. Use ofthe plication technique requires many operational steps and over timesutures have been reported to come loose and/or the tissue folds havediminished or disappeared. Control of the amount and location of bulkingagent delivery remains an art form, and in some cases the agent hasmigrated from its original location. RF delivery with needles requirescareful monitoring of impedance and temperature in the tissue to preventcoagulation around the needle and associated rapid increases intemperature. Lesion size is also limited by the needle size. Limitationsof the design require additional steps of rotating the device to achieveadditional lesions. Physicians have to be careful not to move the deviceduring each of the multiple one-minute energy deliveries to ensure theneedles do not tear the tissue.

Dysfunction of the anal sphincter leads to fecal incontinence, the lossof voluntary control of the sphincter to retain stool in the rectum.Fecal incontinence is frequently a result of childbearing injuries orprior anorectal surgery. In most patients, fecal incontinence isinitially treated with conservative measures, such as biofeedbacktraining, alteration of the stool consistency, and the use of colonicenemas or suppositories. Biofeedback is successful in approximatelytwo-thirds of patients who retain some degree of rectal sensation andfunctioning of the external anal sphincter. However, multiple sessionsare often necessary, and patients need to be highly motivated.Electronic home biofeedback systems are available and may be helpful asadjuvant therapy. Several surgical approaches to fecal incontinence havebeen tried, with varying success, when conservative management hasfailed. These treatments include sphincter repair, gracilis or gluteusmuscle transposition to reconstruct an artificial sphincter, and sacralnerve root stimulation. The approach that is used depends on the causeof the incontinence and the expertise of the surgeon. Surgicalinterventions suffer from the same disadvantages discussed above withrespect to GERD. An RF needle ablation device, similar in design to thatdescribed above for treatment of GERD, has been described inWO/01/80723. Potential device complications and use limitations aresimilar to those described for GERD.

Dysfunction of the urinary sphincter leads to urinary incontinence, theloss of voluntary control of the sphincter to retain urine in thebladder. In women this is usually manifest as stress urinaryincontinence, where urine is leaked during coughing, sneezing, laughing,or exercising. It occurs when muscles and tissues in the pelvic floorare stretched and weakened during normal life events such as childbirth,chronic straining, obesity, and menopause. In men, urinary incontinenceis usually a result of pressure of an enlarged prostate against thebladder.

U.S. Pat. No. 6,073,052 describes a method of sphincter treatment usinga microwave antennae and specific time and temperature ranges, and U.S.Pat. No. 6,321,121 a method of GERD treatment using a non-specificenergy source, with limited enabling specifications. The use ofultrasound energy for circumferential heating of the pulmonary vein tocreate electrical conduction block has been described in U.S. Pat. No.6,012,457 and U.S. Pat. No. 6,024,740. The use of ultrasound for tumortreatments has been described in U.S. Pat. No. 5,620,479.

In view of the foregoing, and notwithstanding the various effortsexemplified in the prior art, there remains a need for a more simple,rapid, minimally invasive approach to treating sphincters that minimizesrisk to the patient.

SUMMARY OF THE INVENTION

The present invention seeks to heat sphincter tissues using ultrasoundenergy. The preferred method is to use ultrasound energy to heat tissueand thus create necrotic regions (lesions) in the tissue. The lesionstighten the tissue by shrinking it (through dessication, proteindenaturation, and disruption of collagen bonds), and/or bulking it (withnew collagen formation). The lesions also prevent or delay opening ofthe sphincter by reducing the compliance of the tissue in either or boththe radial and longitudinal directions as the sphincter is forced toexpand and shorten when the internal pressure increases. The lesionsalso interrupt nerve pathways responsible for sphincter relaxations. Ingeneral, during the heating process, the invention employs means tominimize heat damage to the mucosal layer of the sphincter. However, inthe case of Barrett's Esophagus, selective heating of the intestinalmetaplasia on the luminal surface of the esophagus is preferred.Ultrasound may also be used (continuously or in pulsed mode) to createshock waves that cause mechanical disruption through cavitation thatcreate the desired tissue effects. While this invention relates broadlyto many tissue sphincters in the body, the focus of the disclosure willbe on the treatment of a dysfunctional lower esophageal sphincter (LES)responsible for GERD.

The key advantage of an ultrasound ablation system over others is that auniform annulus of tissue can be heated simultaneously. Alternatively,the transducers can be designed so that only user-defined preciseregions of the circumference are heated. Ultrasound also penetratestissue deeper than RF or simple thermal conduction, and therefore can bedelivered with a more uniform temperature profile. Thus lesions can becreated at deeper locations than could be safely achieved with RFneedles puncturing the tissue. Similarly, the deeper heating and uniformtemperature profile also allow for an improved ability to create acooling gradient at the surface. Relatively low power can be deliveredover relatively long durations to maximize tissue penetration butminimize surface heating. If only surface heating is desired, as in thecase of Barrett's Esophagus, the acoustic energy can be focused at orjust before the tissue surface. Another means to selectively heat thetissue surface is to place a material against the tissue, between thetissue and the transducer, that selectively absorbs acoustic energy andpreferentially heats at the tissue interface. A device using ultrasoundfor ablation may also be configured to allow diagnostic imaging of thetissue to determine the proper location for therapy and to monitor thelesion formation process.

In a first specific aspect of the present invention, methods forremodeling luminal tissue comprise positioning a vibrational transducerat a target site in a body lumen of a patient. The vibrationaltransducer is energized to produce acoustic energy under conditionsselected to induce tissue remodeling in at least a portion of the tissuecircumferentially surrounding the body lumen. In particular, the tissueremodeling may be directed at or near the luminal surface, but will moreusually be directed at a location at a depth beneath the luminalsurface, typically from 1 mm to 10 mm, more usually from 2 mm to 6 mm.In the case of Barrett's Esophagus, the first 1 to 3 mm of tissue depthis to be remodeled. In the most preferred cases, the tissue remodelingwill be performed in a generally uniform matter on a ring or region oftissue circumferentially surrounding the body lumen, as described inmore detail below.

The acoustic energy will typically be ultrasonic energy produced byelectrically exciting an ultrasonic transducer which may optionally becoupled to an ultrasonic horn, resonant structure, or other additionalmechanical structure which can focus or enhance the vibrational acousticenergy. In an exemplary case, the transducer is a phased arraytransducer capable of selectively focusing and/or scanning energycircumferentially around the body lumen.

The acoustic energy is produced under conditions which may have one ormore of a variety of biological effects. In many instances, the acousticenergy will be produced under conditions which cause shrinkage of thetissue, optionally by heating the tissue and inducing shrinkage of thecollagen. Alternatively or additionally, the acoustic energy may beproduced under conditions which induce collagen formation in order tobulk or increase the mass of tissue present. Such collagen formation mayin some cases, at least, result from cavitation or otherinjury-producing application of the vibrational energy. Thus, under someconditions, the vibrational energy will be produced under conditionswhich cause cavitation within the tissues. Additionally, the acousticenergy may be produced under conditions which interrupt nerve pathwayswithin the tissue, such as the vagal nerves as described in more detailhereinafter. Add info here relating to treating intestinal metaplasia,interruption of biochemical reception and production, and prevention offood absorption.

Preferred ultrasonic transducers may be energized to produce unfocusedacoustic energy from the transducer surface in the range from 10W/cm.sup.2 to 100 W/cm.sup.2, usually from 30 W/cm.sup.2 to 70W/cm.sup.2. The transducer will usually be energized at a duty cycle inthe range from 10% to 100%, more usually from 70% to 100%. Focusedultrasound may have much higher energy densities, but will typically useshorter exposure times and/or duty cycles. In the case of heating thetissue, the transducer will usually be energized under conditions whichcause a temperature rise in the tissue to a tissue temperature in therange from 55.degree. C. to 95.degree. C., usually from 60.degree. C. to80.degree. C. In such instances, it will usually be desirable to coolthe luminal surface, which is a mucosal surface in the case of theesophagus which may treated by the present invention, in order to reducethe risk of injury.

Usually, the vibrational transducer will be introduced to the body lumenusing a catheter which carries the transducer. In certain specificembodiments, the transducer will be carried within an inflatable balloonon the catheter, and the balloon when inflated will at least partlyengage the luminal wall in order to locate the transducer at apre-determined position relative to the luminal target site. In aparticular instance, the transducer is disposed within the inflatableballoon, and the balloon is inflated with an acoustically transmissivematerial so that the balloon will both center the transducer and enhancetransmission of acoustic energy to the tissue. In an alternativeembodiment, the transducer may be located between a pair of axiallyspaced-apart balloons. In such instances, when the balloons areinflated, the transducer is centered within the lumen. Usually, anacoustically transmissive medium is then introduced between the inflatedballoons to enhance transmission of the acoustic energy to the tissue.In any of these instances, the methods of the present inventionoptionally comprise moving the transducer relative to the balloons,typically in an axially direction, in order to focus or scan theacoustic energy at different locations on the luminal tissue surface.

In specific embodiments, the acoustically transmissive medium may becooled in order to enhance cooling of the luminal tissue surface.Additionally, the methods may further comprise monitoring temperature ofthe luminal tissue surface and/or at a point beneath the luminal tissuesurface.

In other specific examples, methods of the present invention furthercomprise focusing acoustic energy beneath the luminal tissue surface. Orin the case of Barrett's Esophagus, acoustic energy is focused at orjust before the luminal tissue surface. In such instances, focusing maybe achieved using a phased array (by selectively energizing particularelements of the array) and the tissue may be treated at variouslocations and various depths.

The methods as described above are particularly preferred for treatingpatients suffering from gastroesophageal reflex disease (GERD) where theacoustic energy remodels the tissue surrounding a lower esophagealsphincter (LES). In other instances, the methods of the presentinvention may be used to treat patients suffering hiatal hernias, wherethe acoustic energy is directed at tissue surrounding a diaphragmaticsphincter above the LES, to treat the anal sphincter for incontinentpatients, to remodel tissues of the bladder neck and surroundingendopelvic fascia for urinary stress incontinence, etc. Further, themethods of the present invention can be used to induce feelings ofsatiety in obese patients, where acoustic energy is delivered to regionsof the stomach and small intestine to interrupt or modify vagalmediation of muscle tone, or to block or modify the reception andproduction of biochemicals that affect satiety. The acoustic energy mayalso be used to selectively necrose or shrink tissue in the pylorus todelay gastric emptying and prolong the sensation of fullness. Acousticenergy may also be used to render regions of tissue unable to absorbfood.

The methods of the present invention may further comprise introducing acannula to the target site, expanding a balloon on the cannula at thetarget site with an acoustically transmissive medium, and selectivelydirecting the vibrational transducer within the balloon to remodeltargeted tissue. The balloon can provide a relatively large workingspace and optionally can seal an opening to the body lumen, such as tothe esophagus. Optionally, a viewing scope or other viewing means can beintroduced into the balloon on the cannula to allow visualization of thetissue being treated. In such cases, the acoustically transmissivemedium should also be transparent. Within the inflated balloon, thetransducer on the catheter may be manipulated in a variety of ways,including deflecting, rotating, everting, and the like, in order todirect the vibrational energy precisely where desired. Alternatively oradditionally, phased array and other circumferential array transducersmay be axially translated to otherwise selectively positioned to achievea desired therapy. When used at the end of the esophagus or at anotheropening to a body lumen, the balloon on the cannula may be expanded tocover the entire opening or alternatively may be expanded over alocation adjacent to the opening.

In other embodiments, directing the transducer may comprise selectivelypivoting at least one transducer from a fixed location on the catheteror otherwise within the balloon, optionally comprising deflecting atleast two catheters from spaced-apart locations. In such cases, the twotransducers may be used together in order to focus energy at particularlocation(s) within the target tissue.

In yet another aspect of the present invention, positioning thetransducer may comprise capturing luminal tissue between opposedelements on the catheter where the transducer is disposed on at leastone of the elements. The energy may then be directed from the transducerinto the captured tissue. Capturing may comprise clamping the tissuebetween moveable elements and/or applying a vacuum to the tissue to drawtissue between the opposed elements.

The present invention still further comprises apparatus for remodelingthe lower esophageal sphincter. Such apparatus comprise a catheter orprobe adapted to be esophageally introduced to the lower esophagealsphincter and a vibrational transducer on the catheter. The transduceris adapted to deliver acoustic energy to the tissue of the LES in orderto lessen gastroesophageal reflux. Apparatus for treating othersphincters may also be provided for certain sphincters such as the analsphincter. The apparatus may comprise a more rigid probe instead of ahighly flexible catheter.

Specific apparatus constructions include providing an inflatable balloonon the catheter, where the balloon is adapted when inflated to positionthe catheter within the LES so that the transducer can deliver energy tothe LES. The transducer is usually positioned coaxially within theballoon, and means may be provided for inflating the balloon with anacoustically transmissive medium.

Alternatively, the transducer may be positioned between a pair ofaxially-spaced-apart balloons, where the apparatus will typicallyfurther comprise means for delivering an acoustically transmissivemedium between the balloons. In all instances, the apparatus may furthercomprise means for cooling the acoustically transmissive medium, andmeans for axially translating the transducer relative to the catheter.In certain specific examples, the transducer comprises a phased arraytransducer.

The present invention may further comprise systems including apparatusas set forth above in combination with a cannula having a channel forreceiving and deploying the catheter of the apparatus. Usually, thesystems will further include a viewing scope or other imaging componentwhich is either part of the cannula or introducable through the cannula.

In preferred embodiments, the cannula further comprises an inflatableballoon formed over a distal end thereof, where the catheter isextendable from the cannula into the balloon when the balloon isinflated. In such embodiments, the vibrational transducer on thecatheter is preferably deflectable, rotatable, and/or evertable withinthe balloon when inflated to allow a high degree of selectivepositioning of the transducer. Alternatively, the vibrational transducermay comprise a circumferential array which is axially translatable orotherwise positionable on the catheter when the balloon is inflated.Still further optionally, the transducer(s) may comprise pivotallymounted transducers on the catheter to permit separate or focusedpositioning of the transducers. Still further alternatively, thetransducer(s) may be mounted on a pair of spaced-apart elements on thecatheter, where the elements are configured to receive target tissuetherebetween. Usually, the elements will be movable to clamp tissuetherebetween and/or a vacuum source will be provided on the catheter toselectively draw tissue into the space between the spaced-apartelements.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustration of the tissue structures comprising theesophagus and stomach.

FIG. 2 is an Ultrasound Ablation System for GERD Treatment.

FIG. 3 is an Ultrasound Ablation Catheter.

FIG. 4 a illustrates the diagnostic endoscopic procedure used toidentify the target treatment area.

FIG. 4 b illustrates the delivery of the tissue treatment apparatus.

FIG. 5 illustrates the positioning of the ultrasound transducer andballoon at the region of the lower esophageal sphincter.

FIG. 6 illustrates the positioning of the “rear-directed” ultrasoundtransducer and balloon distal to the lower esophageal sphincter fordelivering energy to the inferior aspect of the lower esophagealsphincter and the cardia.

FIG. 7 is a preferred pattern of completely circumferential lesions.

FIG. 8 is a preferred pattern of groups of discrete lesions formed incircumferential groups.

FIG. 9 is a cylindrical PZT material.

FIG. 10 is an annular array of flat panel transducers and the acousticoutput from the array.

FIG. 11 is isolated active sectors of a transducer formed by isolatingthe plated regions.

FIG. 12 is a selective plating linked with continuous plating ring.

FIG. 13 is a cylindrical transducer with non-resonant channels.

FIG. 14 is a cylindrical transducer with an eccentric core.

FIG. 15 is a cylindrical transducer with curved cross-section andresulting focal region of acoustic energy.

FIG. 16 is an illustration of acoustic output from conical transducers.

FIG. 17 is a longitudinal array of cylindrical transducers.

FIG. 18 is a transducer mounting configuration using metal mounts.

FIG. 19 shows transducer geometry variations used to enhance mountingintegrity.

FIG. 20 is transducer plating variations used to enhance mountingintegrity.

FIG. 21 shows cooling flow through the catheter center lumen, exitingthe tip.

FIG. 22 shows cooling flow recirculating within the catheter centrallumen.

FIG. 23 shows cooling flow circulating within the balloon.

FIG. 24 shows cooling flow circulating within a lumen/balloon coveringthe transducer.

FIG. 25 shows cooling flow circulating between an inner and an outerballoon.

FIG. 26 is an ultrasound ablation element bounded by tandem occludingmembers.

FIG. 27 shows sector occlusion for targeted ablation and cooling.

FIG. 28 shows thermocouples incorporated into proximally slideablesplines positioned over the outside of the balloon.

FIG. 29 shows thermocouples incorporated into splines fixed to the shaftbut tethered to the distal end with an elastic member.

FIG. 30 shows thermocouples attached to the inside of the balloon,aligned with the ultrasound transducer.

FIG. 31 shows thermocouples positioned on the outside of the balloon,aligned with the ultrasound transducer, and routed across the wall andthrough the inside of the balloon.

FIGS. 32 a-32 c show the use of a slit in the elastic encapsulation of athermocouple bonded to the outside of an elastic balloon that allows thethermocouple to become exposed during balloon inflation.

FIG. 33 shows thermocouples mounted on splines between two occludingballoons and aligned with the transducer.

FIG. 34 a is an Ultrasound Ablation System for GERD Treatment thatincludes an ablation catheter with a tip controllable from a memberattached to the distal tip.

FIG. 34 b is an Ultrasound Ablation System for GERD Treatment thatincludes an ablation catheter with a tip optionally controlled via aninternal tensioning mechanism.

FIG. 35 illustrates the deployment of an overtube with balloon over anendoscope.

FIG. 36 illustrates retraction of the endoscope within the balloon ofthe overtube.

FIG. 37 illustrates inflation of the overtube balloon at the region ofthe Lower Esophageal Sphincter (LES).

FIG. 38 a illustrates advancement of the ablation catheter out of theendoscope.

FIG. 38 b illustrates manipulation of the tip of the ablation catheterin order to direct the energy in a particular direction.

FIG. 39 illustrates lesion formation from above the LES using thepreferred system.

FIG. 40 illustrates lesion formation from below the LES using thepreferred system.

FIG. 41 illustrates lesion formation during the forward delivery ofultrasound from a transducer mounted on the tip of the catheter.

FIG. 42 illustrates lesion formation using the preferred catheter withone external pullwire routed through a second open channel of theendoscope. A smaller, simper overtube balloon is also used.

FIG. 43 illustrates lesion formation using a catheter advanced throughan endoscope channel. No overtube is used; instead, a balloon is mountedon the catheter tip which inflates outward from the tip of the shaft.

FIG. 44 illustrates lesion formation using a deflectable or preshapedcatheter advanced out on an endoscope channel. The overtube has a memberextending distally from the distal opening of the overtube. The balloonis mounted at its distal end to the distal end of the member. The memberhas one or more lumens for fluid delivery and guide wire use.

FIG. 45 illustrates the deployment of an overtube having a doughnutshaped balloon.

FIG. 46 illustrates the lesion formation from an ultrasound ablationcatheter positioned inside the doughnut shaped balloon of the overtube.

FIG. 47 illustrates lesion formation from a catheter having either orboth distal and proximal ablation elements mounted within a peanutshaped balloon.

FIGS. 48 a-48 d illustrate alternative means for changing theorientation of the ultrasound transducer.

FIG. 49 a illustrates lesion formation from an ablation catheter whilesealing the distal LES orifice with a balloon catheter.

FIG. 49 b illustrates lesion formation from an ablation catheter whilesealing the distal LES orifice with a balloon catheter and sealing theesophagus proximal to the LES with a balloon on an overtube.

FIG. 49 c illustrates the use of a stasis valve between the overtube andendoscope to prevent fluid from flowing out the lumen between the twodevices.

FIGS. 49 d and 49 e illustrate different embodiments of the stasis valvemounted on the tip of the overtube.

FIG. 50 illustrates lesion formation from an ablation catheter routedthrough 2 available channels in the endoscope while sealing the distalLES orifice with a balloon catheter.

FIG. 51 illustrates lesion formation from an ablation catheter having amembrane surrounding the transducer while a balloon attached to theopposite side of the shaft forcing the transducer against the tissue.

FIGS. 52 a and 52 b illustrate the use of an ablation device that suckstissue in the region of the LES into a chamber where energy deliveredinto captured tissue.

FIGS. 53 a and 53 b illustrate the use of mechanical swivel grips todraw tissue into and hold within an ablation chamber.

FIG. 53 c illustrates the use of wire to press tissue into and holdwithin an ablation chamber.

FIG. 53 d illustrates the use of inflatable doughnuts to press tissueinto and hold within an ablation chamber.

DETAILED DESCRIPTION OF THE INVENTION

This Specification discloses various catheter-based systems and methodsfor treating dysfunction of sphincters and adjoining tissue regions inthe body. The systems and methods are particularly well suited fortreating these dysfunctions in the upper gastrointestinal tract, e.g.,in the lower esophageal sphincter (LES) and adjacent cardia of thestomach. For this reason, the systems and methods will be described inthis context.

Still, it should be appreciated that the disclosed systems and methodsare applicable for use in treating other dysfunctions elsewhere in thebody, which are not necessarily sphincter-related. For example, thevarious aspects of the invention have application in proceduresrequiring treatment of hemorrhoids, or incontinence, or restoringcompliance to or otherwise tightening interior tissue or muscle regions.The systems and methods that embody features of the invention are alsoadaptable for use with systems and surgical techniques that are notnecessarily catheter-based.

In general, this disclosure relates to the ability of the ultrasound toheat the tissue in order to cause it to acutely shrink and tighten. Itshould also be noted that another physiologic means by which the tissuemay move inward after heating is through the stimulation of new collagengrowth during the healing phase. Besides swelling the wall, it may alsoserve to strengthen the wall. Further, by necrosing viable tissue, vagalafferent pathways responsible for transient relaxations of the LES arereduced or eliminated, leading to improved tonic contraction of the LES.

For the purposes of stimulating collagen growth, it may be sufficient todeliver shock waves to the tissue such that the tissue matrix ismechanically disrupted (i.e, via cavitation), but not necessarilyheated. This is another means by which ultrasound could be a morebeneficial energy modality than others. The ultrasound could bedelivered in high-energy MHz pulses or through lower energy kHz or“lithotriptic” levels.

As FIG. 1 shows, the esophagus 10 is an approximately 25 cm longmuscular tube that transports food from the mouth to the stomach 12using peristaltic contractions. Mucous is secreted from the walls of theesophagus to lubricate the inner surface and allow food to pass moreeasily.

The junction of the esophagus 10 with the stomach 12 is controlled bythe lower esophageal sphincter (LES) 18, a thickened circular ring ofsmooth esophageal muscle. The LES straddles the squamocolumnar junction,or z-line 14—a transition in esophageal tissue structure that can beidentified endoscopically. An upper region of the stomach 12 thatsurrounds the LES 18 is referred to as the cardia 20. After food passesinto the stomach 12, the LES 18 constricts to prevent the contents fromregurgitating into the esophagus 10. Muscular contractions of thediaphragm 16 around the esophageal hiatus 17 during breathing serve as adiaphragmatic sphincter that offers secondary augmentation of loweresophageal sphincter pressure to prevent reflux.

The LES 18 relaxes before the esophagus 10 contracts, and allows food topass through to the stomach 12. After food passes into the stomach 12,the LES 18 constricts to prevent the contents from regurgitating intothe esophagus 10. The resting tone of the LES 18 is maintained bymuscular and nerve mechanisms, as well as different reflex mechanisms,physiologic alterations, and ingested substances. Transient LESrelaxations may manifest independently of swallowing. This relaxation isoften associated with transient gastroesophageal reflux in normalpeople.

Dysfunction of the LES 18, typically manifest through transientrelaxations, leads to reflux of stomach acids into the esophagus 10. Oneof the primary causes of the sphincter relaxations is believed to beaberrant vagally-mediated nerve impulses to the LES 18 and cardia 20.This condition, called Gastroesophageal Reflux Disease (GERD), createsdiscomfort such as heartburn and other debilitating symptoms.Dysfunction of the diaphragmatic sphincter (at the esophageal hiatus17), such as that caused by a hiatal hernia, can compound the problem ofLES relaxations.

It should be noted that the views of the esophagus and stomach shown inFIG. 1 and elsewhere in the drawings are not intended to be strictlyaccurate in an anatomic sense. The drawings show the esophagus andstomach in somewhat diagrammatic form to demonstrate the features of theinvention.

As shown in FIG. 2, the present invention relates to an ablation system30 consisting of an ablation device 32 with an acoustic energy deliveryelement (ultrasound transducer) 34 mounted on the distal end of thecatheter. The device is delivered transorally to the region of the LES18. The system 30 consists of the following key components:

1. A catheter shaft 36 with proximal hub 38 containing fluid ports 40,electrical connectors 42, and optional central guidewire lumen port 44.

2. An ultrasound transducer 34 that produces acoustic energy 35 at thedistal end of the catheter shaft 36

3. An expandable balloon 46 operated with a syringe 48 used to create afluid chamber 50 that couples the acoustic energy 35 to the tissue 60

4. Temperature sensor(s) 52 in the zone of energy delivery

5. An energy generator 70 and connector cable(s) 72 for driving thetransducer and displaying temperature values

6. A fluid pump 80 delivering cooling fluid 82.

As shown in FIG. 3, the preferred embodiment of the ablation deviceconsists of an ultrasound transducer 34 mounted within the balloon 46near the distal end of an elongated catheter shaft 36. A proximal hub,or handle, 38 allows connections to the generator 70, fluid pump 80, andballoon inflation syringe 48. In other embodiments (not shown) thehub/handle 38 may provide a port for a guidewire and an actuator fordeflection or spline deployment. The distal tip 39 is made of a soft,optionally preshaped, material such as low durometer silicone orurethane to prevent tissue trauma. The ultrasound transducer 34 ispreferably made of a cylindrical ceramic PZT material, but could be madeof other materials and geometric arrangements as are discussed in moredetail below. Depending on performance needs, the balloon 46 may consistof a compliant material such as silicone or urethane, or a morenon-compliant material such as nylon or PET, or any other materialhaving a compliance range between the two. Temperature sensors 52 arealigned with the beam of acoustic energy 35 where it contacts thetissue. Various configurations of temperature monitoring are discussedin more detail below. The catheter is connected to an energy generator70 that drives the transducer at a specified frequency. The optimalfrequency is dependent on the transducer 34 used and is typically in therange of 7-10 MHz, but could be 1-40 MHz. The frequency may be manuallyentered by the user or automatically set by the generator 70 when thecatheter is connected, based on detection algorithms in the generator.The front panel of the generator 70 displays power levels, deliveryduration, and temperatures from the catheter. A means of detecting anddisplaying balloon inflation volume and/or pressure, and cooling flowrate/pressure may also be incorporated into the generator. Prior toablation, the balloon 46 is inflated with a fluid such as saline orwater, or an acoustic coupling gel, until it contacts the esophagus overa length exceeding the transducer length. Cooling fluid 82 is used tominimize heat buildup in the transducer and keep the mucosal surfacetemperatures in a safe range. In the preferred embodiment shown, coolingfluid 82 is circulated in through the balloon inflation lumen 51 and outthrough the central lumen 53 using a fluid pump 80. As described later,the circulation fluid may be routed through lumens different than theballoon lumen, requiring a separate balloon inflation port 39. Also, itmay be advantageous to irrigate the outer proximal and/or distal end ofthe balloon to cool it and to ensure the expulsion or air on the outeredges of the balloon that could interfere with the coupling of theultrasound into the tissue. The path of this irrigating fluid could befrom a lumen in the catheter and out through ports proximal and/ordistal to the balloon, or from the inner lumen of a sheath placed overthe outside of or alongside the catheter shaft.

In other embodiments (not shown) of the catheter, the central lumen 53could allow passage of a guidewire (i.e., 0.035″) from a proximal port44 out the distal tip 39 for atraumatic placement into the body.Alternatively, a monorail guidewire configuration could be used, wherethe catheter 30 rides on the wire just on the tip section 39 distal tothe transducer 34. A central lumen with open tip configuration wouldalso allow passage of an endoscope for visualization during theprocedure. The catheter could also be fitted with a pull wire connectedto a proximal handle to allow deflection to aid in placement through themouth and down the esophagus. This could also allow deflection of anendoscope in the central lumen. The balloon may also be designed with atextured surface (i.e., adhesive bulbs or ribs) to prevent movement inthe inflated state. Finally, the catheter shaft or balloon or both couldbe fitted with electrodes that allow pacing and electrical signalrecording within the esophagus.

The above ablation device 32 is configured as an elongated catheter. Ofcourse, depending on the sphincter being treated, the ablation devicemay be configured as a probe, or a surgically delivered instrument.

In use (see FIGS. 4 a, 4 b, 5 and 6), the patient lies awake but sedatedin a reclined or semi-reclined position. If used, the physician insertsan esophageal introducer 92 through the throat and partially into theesophagus 10. The introducer 92 is pre-curved to follow the path fromthe mouth, through the pharynx, and into the esophagus 10. Theintroducer 92 also includes a mouthpiece 94, on which the patient bitesto hold the introducer 92 in position. The introducer 92 provides anopen, unobstructed path into the esophagus 10 and prevents spontaneousgag reflexes during the procedure.

The physician need not use the introducer 92. In this instance, a simplemouthpiece 94, upon which the patient bites, is used.

The physician preferably first conducts a diagnostic phase of theprocedure, to localize the site to be treated. As FIG. 4 a shows, avisualization device can be used for this purpose. The visualizationdevice can comprise an endoscope 96, or other suitable visualizingmechanism, carried at the end of a flexible catheter tube 98. Thecatheter tube 98 for the endoscope 96 includes measured markings 97along its length. The markings 97 indicate the distance between a givenlocation along the catheter tube 98 and the endoscope 96.

The physician passes the catheter tube 98 through the patient's mouthand pharynx, and into the esophagus 10, while visualizing through theendoscope 96. Relating the alignment of the markings 97 to themouthpiece 94, the physician can gauge, in either relative or absoluteterms, the distance between the patient's mouth and the endoscope 96 inthe esophagus 10. When the physician visualizes the desired treatmentsite (lower esophageal sphincter 18 or cardia 20) with the endoscope 96,the physician records the markings 97 that align with the mouthpiece 94.

The physician next begins the treatment phase of the procedure. As shownin FIG. 4 b, the physician passes the catheter shaft 36 carrying theultrasound transducer 34 through the introducer 92. For the passage, theexpandable balloon 46 is in its collapsed condition. The physician cankeep the endoscope 96 deployed for viewing the expansion and fit of theballoon 46 with the tissue 60, either separately deployed in aside-by-side relationship with the catheter shaft 36, or (as will bedescribed later) by deployment through a lumen in the catheter shaft 36or advancement of the catheter 32 through a lumen in the endoscope 96itself and expansion of the balloon distal to the endoscope 96. If thereis not enough space for side-by-side deployment of the endoscope 96, thephysician deploys the endoscope 96 before and after expansion of theballoon 46.

As illustrated in FIG. 4 b, the catheter shaft 36 includes measuredmarkings 99 along its length. The measured markings 99 indicate thedistance between a given location along the catheter shaft 36 and theultrasound transducer 34. The markings 99 on the catheter shaft 36correspond in spacing and scale with the measured markings 97 along theendoscope catheter tube 98. The physician can thereby relate themarkings 99 on the catheter shaft 36 to gauge, in either relative orabsolute terms, the location of the ultrasound transducer 34 inside theesophagus 10. When the markings 99 indicate that the ultrasoundtransducer 34 is at the desired location (earlier visualized by theendoscope 96), the physician stops passage of the ultrasound transducer34. The ultrasound transducer 34 is now located at the site targeted fortreatment.

In FIG. 5, the targeted site is shown to be the lower esophagealsphincter 18. In FIG. 6, the targeted site is shown to be the cardia 20of the stomach 12.

Once located at the targeted site, the physician operates the syringe 48to convey fluid or coupling gel into the expandable balloon 46. Theballoon 46 expands to make intimate contact with the mucosal surface,either with the sphincter (see FIG. 5) or the cardia 20 (FIG. 6) over alength longer than where the acoustic energy 35 impacts the tissue. Theballoon is expanded to temporarily dilate the lower esophageal sphincter18 or cardia 20, to remove some or all the folds normally present in themucosal surface, and to create a chamber 50 of fluid or gel throughwhich the acoustic energy 35 couples to the tissue 60. The expandedballoon 46 also places the temperature sensors 52 in intimate contactwith the mucosal surface.

The physician commands the energy generator 70 to apply electricalenergy to the ultrasound transducer 34. The function of the ultrasoundtransducer 34 is to then convert the electrical energy to acousticenergy 35.

The energy heats the smooth muscle tissue below the mucosal lining. Thegenerator 70 displays temperatures sensed by the temperature sensors 80to monitor the application of energy. The physician may choose to reducethe energy output of the generator 70 if the temperatures exceedpredetermined thresholds. The generator 70 may also automaticallyshutoff the power if temperature sensors 80 or other sensors in thecatheter exceed safety limits.

Prior to energy delivery, it will most likely be necessary for thephysician to make use of a fluid pump 80 to deliver cooling fluid 82 tokeep the mucosal temperature below a safe threshold. This is discussedin more detail later. The pump 80 may be integrated into the generatorunit 70 or operated as a separate unit.

Preferably, for a region of the lower esophageal sphincter 18 or cardia20, energy is applied to achieve tissue temperatures in the smoothmuscle tissue in the range of 55.degree. C. to 95.degree. C. In thisway, lesions can typically be created at depths ranging from one 1 mmbelow the mucosal surface to as far as the outside wall of the esophagus10. Typical acoustic energy densities range 10 to 100 W/cm.sup.2 asmeasured at the transducer surface. For focusing elements, the acousticenergy densities at the focal point are much higher.

It is desirable that the lesions possess sufficient volume to evoketissue-healing processes accompanied by intervention of fibroblasts,myofibroblasts, macrophages, and other cells. The healing processesresults in a contraction of tissue about the lesion, to decrease itsvolume or otherwise alter its biomechanical properties. Replacement ofcollagen by new collagen growth may also serve to bulk the wall of thesphincter. The healing processes naturally tighten the smooth muscletissue in the sphincter 18 or cardia 20. Ultrasound energy typicallypenetrates deeper than is possibly by RF heating or thermal conductionalone.

With a full circumferential output of acoustic energy 35 from ultrasoundtransducer 34, it is possible to create a completely circumferentiallesion 100 in the tissue 60 of the LES 18. To create greater lesiondensity in a given targeted tissue area, it is also desirable to createa pattern of multiple circumferential lesions 102 a spaced axially alongthe length of the targeted treatment site in the LES 18 or cardia 20(above and below the z-line 14, as shown in FIG. 7. Preferably, apattern of 4 circumferential lesions 102 a is desired spaced 1 cm apart,with 2 above the z-line 14, and 2 below; however, the safe and effectiverange may be just one or higher, depending on how the lesions form andheal. As shown in FIG. 6, the use of a “rear directed” ultrasound beamalso allows treatment of the inferior aspect of the LES 18 and thecardia 20.

To limit the amount of tissue ablated, and still achieve the desiredeffect, it may be beneficial to spare and leave viable somecircumferential sections of the esophageal wall. To this end, theultrasound transducer 34 can be configured (embodiments of which arediscussed in detail below) to emit ultrasound in discrete locationsaround the circumference. Various lesion patterns 102 b can be achieved.A preferred pattern (shown in FIG. 8 for the esophagus 10) comprisesseveral rings 104 of lesions 106 about 5 mm apart, each ring 104comprising preferably 8 (potential range 1-16) lesions 106. For example,a preferred pattern 102 b comprises six rings 104, 3 above and 3 belowthe z-line 14, each with eight lesions 106.

The physician can create a given ring pattern (either fullycircumferential lesions or discrete lesions spaced around thecircumference) 100 by expanding the balloon 46 with fluid or gel,pumping fluid 82 to cool the mucosal tissue interface as necessary, anddelivering electrical energy from the generator 70 to produce acousticenergy 35 to the tissue 90. The lesions in a given ring (100 or 104) canbe formed simultaneously with the same application of energy, orone-by-one, or in a desired combination. Additional rings of lesions canbe created by advancing the ultrasound transducer 34 axially, gaugingthe ring separation by the markings 99 on the catheter shaft 36. Other,more random or eccentric patterns of lesions can be formed to achievethe desired density of lesions within a given targeted site.

The catheter 32 can also be configured such that once the balloon 46 isexpanded in place, the distal shaft 36 upon which the transducer 34 ismounted can be advanced axially within the balloon 46 that creates thefluid chamber 35, without changing the position of the balloon 46.Preferably, the temperature sensor(s) 52 move with the transducer 34 tomaintain their position relative to the energy beam 35.

The distal catheter shaft 36 can also be configured with multipleultrasound transducers 34 and temperature sensors 52 along the distalaxis in the fluid chamber 35 to allow multiple rings to be formedsimultaneously or in any desired combination. They can also simply beformed one-by-one without having to adjust the axial position of thecatheter 32.

To achieve certain heating effects, it may be necessary to utilizevariations of the transducer, balloon, cooling system, and temperaturemonitoring. For instance, in order to prevent ablation of the mucosallining of the esophagus 10, it may be necessary to either (or both)focus the ultrasound under the surface, or sufficiently cool the surfaceduring energy delivery. To treat Barrett's Esophagus, the ultrasound maybe focused at or just before the tissue surface. The balloon material,or an additional material adjacent to the balloon between the tissue andthe transducer may be made of sufficient dimensions and acousticproperties to selectively absorb energy at the tissue interface.Materials having good acoustic absorption properties include siliconeand polyurethane rubbers, and oil suspensions. Increasing the frequencyof the transducer will also aid in confining acoustic absorption at thesurface. Temperature monitoring provides feedback as to the how well thetissue is being heated and cooled.

The following sections describe various embodiments of the ultrasoundtransducer 34 design, the mounting of the ultrasound transducer 34,cooling configurations, and means of temperature monitoring.

Ultrasound Transducer Design Configurations: In one preferredembodiment, shown in FIG. 9, the transducer 34 is a cylinder of PZT(i.e., PZT-4, PZT-8) material 130. The material is plated on the insideand outside with a conductive metal, and poled to “flip”, or align, thedipoles in the PZT material 130 in a radial direction. This plating 120allows for even distribution of an applied potential across the dipoles.It may also be necessary to apply a “seed” layer (i.e., sputtered gold)to the PZT 130 prior to plating to improve plating adhesion. The dipoles(and therefore the wall of the material) stretch and contract as theapplied voltage is alternated. At or near the resonant frequency,acoustic waves (energy) 35 emanate in the radial direction from theentire circumference of the transducer. The length of the transducer canbe selected to ablate wide or narrow regions of tissue. The cylinder is5 mm long in best mode, but could be 2-20 mm long. Inner diameter is afunction of the shaft size on which the transducer is mounted, typicallyranging from 1 to 4 mm. The wall thickness is a function of the desiredfrequency. An 8 MHz transducer would require about a 0.011″ thick wall.

In another embodiment of the transducer 34 design, illustrated in FIG.10, multiple strips 132 of PZT 130 or MEMS (Micro Electro MechanicalSystems—Sensant, Inc., San Leandro, Calif.) material are positionedaround the circumference of the shaft to allow the user to ablateselected sectors. The strips 132 generally have a rectangular crosssection, but could have other shapes. Multiple rows of strips could alsobe spaced axially along the longitudinal axis of the device. By ablatingspecific regions, the user may avoid collateral damage in sensitiveareas, or ensure that some spots of viable tissue remain around thecircumference after energy delivery. The strips 132 may be all connectedin parallel for simultaneous operation from one source, individuallywired for independent operation, or a combination such that some stripsare activated together from one wire connection, while the others areactivated from another common connection. In the latter case, forexample, where 8 strips are arranged around the circumference, everyother strip (every 90.degree.) could be activated at once, with theremaining strips (90.degree. C. apart, but 45.degree. C. from theprevious strips) are activated at a different time. Another potentialbenefit of this multi-strip configuration is that simultaneous or phasedoperation of the strips 132 could allow for regions of constructiveinterference (focal regions 140) to enhance heating in certain regionsaround the circumference, deeper in the tissue. Phasing algorithms couldbe employed to enhance or “steer” the focal regions 140. Each strip 132could also be formed as a curved x-section or be used in combinationwith a focusing lens to deliver multiple focal heating points 140 aroundthe circumference.

The use of multiple strips 132 described above also allows thepossibility to use the strips for imaging. The same strips could be usedfor imaging and ablation, or special strips mixed in with the ablationstrips could be used for imaging. The special imaging strips may also beoperated at a different frequency than the ablation strips. Sincespecial imaging strips use lower power than ablation strips, they couldbe coated with special matching layers on the inside and outside asnecessary, or be fitted with lensing material. The use of MEMs stripsallows for designs where higher resolution “cells” on the strips couldbe made for more precise imaging. The MEMs design also allows for amixture of ablation and imaging cells on one strip. Phasing algorithmscould be employed to enhance the imaging.

In another embodiment of the transducer 34 design, shown in FIG. 11, asingle cylindrical transducer 34 as previously described is subdividedinto separate active longitudinal segments 134 arrayed around thecircumference through the creation of discrete regions of inner plating124 and outer plating 126. To accomplish this, longitudinal segments ofthe cylindrical PZT material 130 could be masked to isolate regions 127from one another during the plating process (and any seed treatment, asapplicable). Masking may be accomplished by applying wax, or by pressinga plastic material against the PZT 130 surface to prevent platingadhesion. Alternatively, the entire inner and outer surface could beplated followed by selective removal of the plating (by machining,grinding, sanding, etc.). The result is similar to that shown in FIG.10, with the primary difference being that the transducer is notcomposed of multiple strips of PZT 130, but of one continuous unit ofPZT 130 that has different active zones electrically isolated from oneanother. Ablating through all at once may provide regions ofconstructive interference (focal regions 140) deeper in the tissue.Phasing algorithms could also be employed to enhance the focal regions140.

As described above, this transducer 34 can also be wired and controlledsuch that the user can ablate specific sectors, or ablate through allsimultaneously. Different wiring conventions may be employed. Individual“+” and “−” leads may be applied to each pair of inner 124 and outer 126plated regions. Alternatively, a common “ground” may be made by eithershorting together all the inner leads, or all the outer leads and thenwiring the remaining plated regions individually.

Similarly, it may only be necessary to mask (or remove) the plating oneither the inner 124 or the outer 126 layers. Continuous plating on theinner region 124, for example, with one lead extending from it, isessentially the same as shorting together the individual sectors.However, there may be subtle performance differences (either desirableor not) created when poling the device with one plating surfacecontinuous and the other sectored.

In addition to the concept illustrated in FIG. 11, it may be desirableto have a continuous plating ring 128 around either or both ends of thetransducer 34, as shown in FIG. 12 (continuous plating shown on theproximal outer end only, with no discontinuities on the inner plating).This arrangement could be on either or both the inner and outer platingsurface. This allows for one wire connection to drive the giventransducer surface at once (the concept in FIG. 11 would requiremultiple wire connections).

Another means to achieve discrete active sectors in a single cylinder ofPZT is to increase or decrease the wall thickness (from the resonantwall thickness) to create non-resonant and therefore inactive sectors.The entire inner and outer surface can be then plated after machining.As illustrated in FIG. 13, channels 150 are machined into the transducerto reduce the wall thickness from the resonant value. As an example, ifthe desired resonant wall thickness is 0.0110″, the transducer can bemachined into a cylinder with a 0.0080″ wall thickness and then havechannels 150 machined to reduce the wall thickness to a non-resonantvalue (i.e., 0.0090″). Thus, when the transducer 34 is driven at thefrequency that resonates the 0.0110″ wall, the 0.0090″ walls will benon-resonant. Or the transducer 34 can be machined into a cylinder witha 0.015″ wall thickness, for example, and then have selective regionsmachined to the desired resonant wall thickness of, say, 0.0110″. Sometransducer PZT material is formed through an injection molding orextrusion process. The PZT could then be formed with the desiredchannels 150 without machining.

Another way to achieve the effect of a discrete zone of resonance is tomachine the cylinder such that the central core 160 is eccentric, asshown in FIG. 14. Thus different regions will have different wallthicknesses and thus different resonant frequencies.

It may be desirable to simply run one of the variable wall thicknesstransducers illustrated above at a given resonant frequency and allowthe non-resonant walls be non-active. However, this does not allow theuser to vary which circumferential sector is active. As a result, it maybe desirable to also mask/remove the plating in the configurations withvariable wall thickness and wire the sectors individually.

In another method of use, the user may gain control over whichcircumferential sector is active by changing the resonant frequency.Thus the transducer 34 could be machined (or molded or extruded) todifferent wall thicknesses that resonate at different frequencies. Thus,even if the plating 122 is continuous on each inner 124 and outer 126surface, the user can operate different sectors at differentfrequencies. This is also the case for the embodiment shown in FIG. 10where the individual strips 132 could be manufactured into differentresonant thicknesses. There may be additional advantages of ensuringdifferent depths of heating of different sectors by operating atdifferent frequencies. Frequency sweeping or phasing may also bedesirable.

For the above transducer designs, longitudinal divisions are discussed.It is conceivable that transverse or helical divisions would also bedesirable. Also, while the nature of the invention relates to acylindrical transducer, the general concepts of creating discrete zonesof resonance can also be applied to other shapes (planar, curved,spherical, conical, etc.). There can also be many different platingpatterns or channel patterns that are conceivable to achieve aparticular energy output pattern or to serve specific manufacturingneeds.

Except where specifically mentioned, the above transducer embodimentshave a relatively uniform energy concentration as the ultrasoundpropagates into the tissue. The following transducer designs relate toconfigurations that focus the energy at some depth. This is desirable tominimize the heating of the tissue at the mucosal surface but create alesion at some depth.

One means of focusing the energy is to apply a cover layer “lens” 170(not shown) to the surface of the transducer in a geometry that causesfocusing of the acoustic waves emanating from the surface of thetransducer 34. The lens 170 is commonly formed out an acousticallytransmissive epoxy that has a speed of sound different than the PZTmaterial 130 and/or surrounding coupling medium. The lens 170 could beapplied directly to the transducer, or positioned some distance awayfrom it. Between the lens 170 and the transducer may be a couplingmedium of water, gel, or similarly non-attenuating material. The lenscould be suspended over (around) the transducer 34 within the balloon46, or on the balloon itself.

In another embodiment, the cylindrical transducer 34 can be formed witha circular or parabolic cross section. As illustrated in FIG. 15, thisdesign allows the beam to have focal regions 140 and cause higher energyintensities within the wall of the tissue.

In another embodiment shown in FIG. 16, angled strips or angled rings(cones) allow forward and/or rear projection of ultrasound (acousticenergy 35). Rearward projection of ultrasound 35 may be particularlyuseful to heat the underside of the LES 18 or cardia 20 when thetransducer element 34 is positioned distal to the LES 18. Each conecould also have a concave or convex shape, or be used with a lensingmaterial 170 to alter the beam shape. In combination with opposingangled strips or cones (forward 192 and rearward 194) the configurationallows for focal zones of heating 140.

In another embodiment, shown in FIG. 17, multiple rings (cylinders) ofPZT transducers 34 would be useful to allow the user to change theablation location without moving the catheter. This also allows forregions of constructive/destructive interference (focal regions 140)when run simultaneously. Anytime multiple elements are used, the phaseof the individual elements may be varied to “steer” the most intenseregion of the beam in different directions. Rings could also have aslight convex shape to enhance the spread and overlap zones, or aconcave shape to focus the beam from each ring. Pairs of opposing conesor angled strips (described above) could also be employed. Each ringcould also be used in combination with a lensing material 170 to achievethe same goals.

Transducer Mounting: One particular challenge in designing transducersthat deliver significant power (approximately 10 acoustic watts percm.sup.2 at the transducer surface, or greater) is preventing thedegradation of adhesives and other heat/vibration sensitive materials inproximity to the transducer. If degradation occurs, materials under orover the transducer can delaminate and cause voids that negativelyaffect the acoustic coupling and impedance of the transducer. In caseswhere air backing of the transducer is used, material degradation canlead to fluid infiltration into the air space that will compromisetransducer performance. Some methods of preventing degradation aredescribed below.

In FIG. 18, a preferred means of mounting the transducer 34 is tosecurely bond and seal (by welding or soldering) the transducer to ametal mounting member 200 that extends beyond the transducer edges.Adhesive attachments 202 can then be made between the mounting member200 extensions remote to the transducer 34 itself. The mountingmember(s) can provide the offsets from the underlying mounting structure206 necessary to ensure air backing between the transducer 34 and theunderlying mounting structure 206. One example of this is shown in FIG.18 where metal rings 200 are mounted under the ends of the transducer34. The metal rings 200 could also be attached to the top edges of thetransducer 34, or to a plated end of the transducer. It may also bepossible to mechanically compress the metal rings against the transduceredges. This could be accomplished through a swaging process or throughthe use of a shape-memory material such as nitenol. It may also bepossible to use a single metal material under the transducer as themounting member 200 that has depressions (i.e. grooves, holes, etc.) inthe region under the transducer to ensure air backing. A porous metal orpolymer could also be placed under the transducer 34 (with the option ofbeing in contact with the transducer) to provide air backing.

In FIG. 19, another means of mounting the transducer 34 is to form thetransducer 34 such that non-resonating portions 210 of the transducer 34extend away from the central resonant section 212. The benefit is thatthe non-resonant regions 210 are integral with the resonant regions 212,but will not significantly heat or vibrate such that they can be safelyattached to the underlying mounting structure 206 with adhesives 202.This could be accomplished by machining a transducer 34 such that theends of the transducer are thicker (or thinner) than the center, asshown in FIG. 19.

As shown in FIG. 20, another option is to only plate the regions of thetransducer 34 where output is desired, or interrupt the plating 122 suchthat there is no electrical conduction to the mounted ends 214(conductor wires connected only to the inner plated regions).

The embodiments described in FIGS. 18-20 can also be combined asnecessary to optimize the mounting integrity and transducer performance.

Cooling Design Configurations: Cooling flow may be necessary to 1)Prevent the transducer temperature from rising to levels that may impairperformance, and 2) Prevent the mucosal lining of the sphincter fromheating to the point of irreversible damage. The following embodimentsdescribe the various means to meet these requirements.

FIG. 21 shows cooling fluid 82 being passed through a central lumen 53and out the distal tip 37 to prevent heat buildup in the transducer 34.The central column of fluid 82 serves as a heat sink for the transducer34.

FIG. 22 is similar to FIG. 21 except that the fluid 82 is recirculatedwithin the central lumen 53 (actually a composition of two or morelumens), and not allowed to pass out the distal tip 37.

FIG. 23 (also shown a part of the preferred embodiment of FIG. 2) showsthe fluid circulation path involving the balloon itself. The fluidenters through the balloon inflation lumen 51 and exits through one ormore ports 224 in the central lumen 53, and then passes proximally outthe central lumen 53. The advantage of this embodiment is that theballoon 46 itself is kept cool, and draws heat away from the mucosallining of the sphincter. Pressure of the recirculating fluid 82 wouldhave to be controlled within a tolerable range to keep the balloon 46inflated the desired amount. Conceivably, the central lumen 53 could bethe balloon inflation lumen, with the flow reversed with respect to thatshown in FIG. 23. Similarly, the flow path does not necessarily requirethe exit of fluid in the central lumen 53 pass under the transducer34—fluid 82 could return through a separate lumen located proximal tothe transducer.

In another embodiment (not shown), the balloon could be made from aporous material that allowed the cooling fluid to exit directly throughthe wall of the balloon. Examples of materials used for the porousballoon include open cell foam, ePTFE, porous urethane or silicone, or apolymeric balloon with laser-drilled holes. It is also conceivable thatif a conductive media, such as saline is used for the cooling fluid, anda ground patch attached to the patient, electrical RF energy from theouter plating of the transducer could be allowed to pass into thetissues and out to the ground patch, resulting in a combination ofacoustic and RF heating of the tissue.

FIG. 24 shows the encapsulation of the transducer 34 within anotherlumen 240. This lumen 240 is optionally expandable, formed from acompliant or non-compliant balloon material 242 inside the outer balloon46 (the lumen for inflating the outer balloon 46 is not shown). Thisallows a substantial volume of fluid to be recirculated within the lumen240 without affecting the inflation pressure/shape of the outer balloon46 in contact with the sphincter. Allowing a substantial inflation ofthis lumen decreases the heat capacity of the fluid in the balloon incontact with the sphincter and thus allows for more efficient cooling ofthe mucosal lining. Fluid 82 could also be allowed to exit the distaltip. It can also be imagined that a focusing lens material 170previously described could be placed on the inner or outer layer of thelumen material 242 surrounding the transducer 34.

As is shown in FIG. 25, there can be an outer balloon 46 that allowscirculation over the top of the inner balloon 242 to ensure rapidcooling at the interface. To ensure flow between the balloons, the innerballoon 242 can be inflated to a diameter less than the outer balloon46. Flow 82 may be returned proximally or allowed to exit the distaltip. Another version of this embodiment could make use of raisedstandoffs 250 (not shown) either on the inside of the outer balloon 46or the outside of the inner balloon 242, or both. The standoffs 250could be raised bumps or splines. The standoffs 250 could be formed inthe balloon material itself, from adhesive, or material placed betweenthe balloons (i.e., plastic or metal mandrels). The standoffs 250 couldbe arranged longitudinally or circumferentially, or both. While notshown in a figure, it can be imagined that the outer balloon 46 shown inFIG. 25 may only need to encompass one side (i.e., the proximal end) ofthe inner balloon, allowing sufficient surface area for heat convectionaway from the primary (inner) balloon 242 that in this case may be incontact with the tissue. In the case of treating Barrett's Esophagus,the space between the two balloons may be filled with an oil suspensionor other fluidic or thixotropic medium that has relatively high acousticattenuation properties. The medium does not necessarily need torecirculate. The intent is that this space between the balloons willpreferentially heat and necrose the intestinal metaplasia lining theesophagus.

In another embodiment, illustrated in FIG. 26, occluding members 260 arepositioned proximal (260 a) and distal (260 b) to the transducer elementfor occluding the sphincter lumen 270. The occluding members 260 mayalso serve to dilate the sphincter region to a desired level. Theoccluding members 260 are capable of being expanded from a collapsedposition (during catheter delivery) for occlusion. Each occluding member260 is preferably an inflatable balloon, but could also be aself-expanding disk or foam material, or a wire cage covered in apolymer, or combination thereof. To deploy and withdraw a non-inflatableoccluding member, either a self-expanding material could be expanded andcompressed when deployed out and back in a sheath, or the occludingmember could be housed within a braided or other cage-like material thatcould be alternatively cinched down or released using a pull mechanismtethered to the proximal end of the catheter 30. It may also bedesirable for the occluding members 260 to have a “textured” surface toprevent slippage of the device. For example, adhesive spots could beapplied to the outer surface of the balloon, or the self-expanding foamcould be fashioned with outer ribs.

With the occluding members 260 expanded against the sphincter lumen, thechamber 278 formed between the balloons is then filled with a fluid orgel 280 that allows the acoustic energy 35 to couple to the tissue 60.To prevent heat damage to the mucosal lining ML of the tissue lumen 270,the fluid/gel 280 may be chilled and/or recirculated. Thus with cooling,the lesion formed within a target site T the tissue 60 is confinedinside the tissue wall and not formed at the inner surface. Thiscooling/coupling fluid 280 may be routed into and out of the spacebetween the occluding members with single entry and exit port, or with aplurality of ports. The ports can be configured (in number, size, andorientation) such that optimal or selective cooling of the mucosalsurface is achieved. Note also that cooling/coupling fluid 280 routedover and/or under the transducer 34 helps keep the transducer cool andhelp prevent degradation in performance.

The transducer element(s) 34 may be any of those previously described.Output may be completely circumferential or applied at select regionsaround the circumference. It is also conceivable that other energysources would work as well, including RF, microwave, laser, andcryogenic sources.

In the case where only certain sectors of tissue around thecircumference are treated, it may be desirable to utilize anotherembodiment, shown in FIG. 27, of the above embodiment shown in FIG. 26.In addition to occluding the proximal and distal ends, such a designwould use a material 290 to occlude regions of the chamber 278 formedbetween the distal and proximal occluding members 260. This would, ineffect, create separate chambers 279 around the circumference betweenthe distal and proximal occluding members 260, and allow for morecontrolled or greater degrees of cooling where energy is applied. Thematerial occluding the chamber could be a compliant foam material or aninflatable balloon material attached to the balloon and shaft. Thetransducer would be designed to be active only where the chamber is notoccluded.

Temperature Monitoring: The temperature at the interface between thetissue and the balloon may be monitored using thermocouples,thermistors, or optical temperature probes. Although any one of thesecould be used, for the illustration of various configurations below,only thermocouples will be discussed. The following concepts could beemployed to measure temperature.

In one embodiment shown in FIG. 28, one or more splines 302, supportingone or more temperature sensors 52 per spline, run longitudinally overthe outside of the balloon 46. On each spline 302 are routed one or morethermocouple conductors (actually a pair of wires) 306. The temperaturesensor 52 is formed at the electrical junction formed between each wirepair in the conductor 306. The thermocouple conductor wires 306 could bebonded straight along the spline 302, or they could be wound or braidedaround the spline 302, or they could be routed through a central lumenin the spline 302.

At least one thermocouple sensor 52 aligned with the center of theultrasound beam 35 is desired, but a linear array of thermocouplesensors 52 could also be formed to be sure at least one sensor 52 in thearray is measuring the hottest temperature. Software in the generator 70may be used to calculate and display the hottest and/or coldesttemperature in the array. The thermocouple sensor 52 could be inside orflush with the spline 302; however, having the sensor formed in a bulbor prong on the tissue-side of the spline 302 is preferred to ensure itis indented into the tissue. It is also conceivable that a thermocoupleplaced on a slideable needle could be used to penetrate the tissue andmeasure the submucosal temperature.

Each spline 302 is preferably formed from a rigid material for adequatetensile strength, with the sensors 52 attached to it. Each individualspline 302 may also be formed from a braid of wires or fibers, or abraid of the thermocouple conductor wires 306 themselves. The splines302 preferably have a rectangular cross section, but could also be roundor oval in cross section. To facilitate deployment and alignment, thesplines 302 may be made out a pre-shaped stainless steel or nitenolmetal. One end of the spline 302 would be fixed to the catheter tip 37,while the proximal section would be slideable inside or alongside thecatheter shaft 36 to allow it to move with the balloon 46 as the ballooninflates. The user may or may not be required to push the splines 302(connected to a proximal actuator, not shown) forward to help themexpand with the balloon 46.

The number of longitudinal splines could be anywhere from one to eight.If the transducer 34 output is sectored, the splines 302 ideally alignwith the active transducer elements.

In a related embodiment, a braided cage (not shown) could be substitutedfor the splines 302. The braided cage would be expandable in a mannersimilar to the splines 302. The braided cage could consist of any or acombination of the following: metal elements for structural integrity(i.e., stainless steel, nitenol), fibers (i.e., Dacron, Kevlar), andthermocouple conductor wires 306. The thermocouple sensors 52 could bebonded to or held within the braid. For integrity of the braid, it maybe desirable for the thermocouple conductors 306 to continue distal tothe thermocouple junction (sensor) 52. The number structural elements inthe braid may be 4 to 24.

In another embodiment shown in FIG. 29, a design similar to theembodiment above is used, except the distal end of the spline 302 isconnected to a compliant band 304 that stretches over the distal end ofthe balloon as the balloon inflates. The band 304 may be formed out of alow durometer material such as silicone, urethane, and the like. It mayalso be formed from a wound metal spring. The spline 302 proximal to theballoon may then be fixed within the catheter shaft 36. Of course thearrangement could be reversed with the spline 302 attached to the distalend of the balloon 46, and the compliant band 304 connected to theproximal shaft 36.

In another embodiment shown in FIG. 30, the sensors 52 are bonded withadhesive 308 to the inside of the balloon (in the path of the ultrasoundbeam 35). The adhesive 308 used is ideally a compliant material such assilicone or urethane if used with a compliant balloon. It may also be acyanoacrylate, epoxy, or UV cured adhesive. The end of the conductorwire 306 at the location of the sensor 52 is preferably shaped into aring or barb or the like to prevent the sensor from pulling out of theadhesive. Multiple sensors 52 may be arranged both circumferentially andlongitudinally on the balloon 46 in the region of the ultrasound beam35. Thermocouple conductor wires 306 would have sufficient slack insidethe balloon 46 to expand as the balloon inflates.

In another embodiment (not shown), the thermocouple conductor wires arerouted longitudinally through the middle of the balloon wall insidepreformed channels.

In another embodiment shown in FIG. 31, the thermocouple sensors 52 arebonded to the outside of the balloon 46, with the conductor wires 306routed through the wall of the balloon 46, in the radial direction, tothe inside of the balloon 46 and lumens in the catheter shaft 36. Theconductor wires 306 would have sufficient slack inside the balloon toexpand as the balloon inflates. To achieve the wire routing, a smallhole is punched in the balloon material, the conductor wire routedthrough, and the hole sealed with adhesive. The conductor wire could becoated in a material that is bondable with the balloon (i.e., theballoon material itself, or a compatible adhesive 308 as described forFIG. 30) prior to adhesive bonding to help ensure a reliable seal.

In another embodiment shown in FIGS. 32 a-32 c, the thermocouple sensors52 mounted on the outer surface of the balloon (regardless of how thewires 306 are routed) are housed in raised bulbs 310 of adhesive 308 (ora molded section of the balloon material itself) that help ensure theyare pushed into the tissue, allowing more accurate tissue temperaturemeasurement that is less susceptible to the temperature gradient createdby the fluid in the balloon. For compliant balloons, a stiff exposedsensor 52 could be housed in a bulb of compliant material with a split312. As the balloon 46 inflates, the split 312 in the bulb 210 opens andexposes the sensor 52 to the tissue. As the balloon 46 deflates, thebulb 310 closes back over the sensor 52 and protects it during cathetermanipulation in the body.

In another embodiment (not shown), an infrared sensor pointed toward theheat zone at the balloon-tissue interface could be configured inside theballoon to record temperatures in a non-contact means.

For the embodiments described in either FIG. 26 or FIG. 27 above, it mayalso be desirable to monitor the temperature of the tissue during energydelivery.

This would be best accomplished through the use of thermocouples alignedwith the ultrasound beam emanating from the transducer. Eachthermocouple would monitor the temperature of the mucosal surface toensure that the appropriate amount of power is being delivered. Powercan be decreased manually or though a feedback control mechanism toprevent heat damage to the mucosa, or the power can be increased to apredetermined safe mucosal temperature rise to ensure adequate power isbeing delivered to the submucosa.

As shown in FIG. 33, the thermocouple sensors 52 could be mounted onsplines 302 similar in design, construction, and operation to thosedescribed previously. In this configuration, the splines 302 areexpanded against the tissue without the use of an interior balloon. Theyare deployed before, during, or after the occlusion members 260 areexpanded. The braided cage configuration described above may also beused.

In another embodiment (not shown), the splines 302 or braided cagecontaining the thermocouple sensors 52 could span over the top of eitheror both expandable occlusive members 260. If the occlusive members 260are balloons, the balloons act to expand the cage outward and againstthe tissue. If the occlusive members 206 are made from a self-expandingfoam or disk material, the cage can be used to contain the occlusivematerial 206 during advancement of the catheter by holding theindividual components of the cage down against the shaft under tension.Once positioned at the site of interest, the cage can be manuallyexpanded to allow the occlusive members 260 to self-expand.

The direction of ultrasound delivery to this point has mostly beendescribed as moving radially into the tissues of the esophagus, LES,and/or gastric cardia. Other system embodiments described below may beemployed to aid in using an ablation device that delivers energy in avariety of directions into the tissue. For example, the ablation devicecan be oriented such that the energy is applied through the longitudinalaxis of the sphincter wall, as opposed to radially through the wall.This has the advantage of preventing energy from passing through theouter wall where surrounding structures, such as the vagal nerves,liver, aorta, and mediastinum reside. In addition, longitudinal lesionsmay help reduce the axial compliance of the sphincter, preventing itfrom shortening and thus delaying how soon it opens as the gastricpressure increases. The designs also lend themselves to use of a planaror partial arc transducer that can be more reliably fabricated into athinner wall than a cylindrical (for circumferential output) transducer.This allows for operation at higher frequencies that increases energyattenuation in the tissue and limits the depth of penetration of theultrasound energy. In this instance, radial direction of the energy ismore feasible without damage to collateral structures. Finally,particular embodiments of this invention may make lesion formation inthe gastric cardia easier than is possible with a circumferentialsystem. Lesions created on the “underside” of the sphincter in theregion of the gastric cardia may help reduce the compliance of thegastric sling fibers in this region. This may help delay opening of thesphincter as the stomach expands due to increases in gastric pressure.The region of the gastric cardia may also have more vagal innervationresponsible for transient relaxations of the sphincter; the lesionswould reduce this innervation.

As shown in FIG. 34 a, the present invention relates to an ablationsystem 400 consisting of an ablation catheter 32 with an acoustic energydelivery element (ultrasound transducer) 34 mounted on the distal end ofthe catheter. The device is delivered transorally to the region of theLES 18. The system 400 consists of the following key components:

1. An overtube 500 having a balloon 502 attached to the distal opening503.

2. An endoscope 96 having at least one therapeutic channel 518 greaterthan 2.8 mm.

3. A catheter 32 having a shaft 36 and a proximal hub/handle 38containing fluid ports 40, electrical connectors 42, and optionalcentral guidewire lumen port 44. The catheter also has an ultrasoundtransducer 34 on a mounting 37 that produces acoustic energy 35 at thedistal end of the distal catheter shaft 520

4. An energy generator 70 and connector cable(s) 72 for driving thetransducer and displaying temperature values

5. A fluid pump 80 delivering cooling fluid 82.

FIG. 34 b illustrates a similar system where the ablation catheter 32makes use of a transducer 34 designed to deliver acoustic energyradially (either circumferentially or in one or more discrete sectors)from the longitudinal axis. The catheter 32 can be moved with respect tothe overtube balloon 502. The tip of the catheter may also bedeflectable from an actuator on the proximal hub/handle 38.

While use of the catheter 32 through a channel in the endoscope 96 ispreferred, it is conceivable that the catheter 32 could be deployedthrough the overtube 500 without the use of the endoscope 96.

The preferred method of ablation treatment is illustrated in FIGS.35-39. In FIG. 35, an overtube device 500 having a peanut-shaped balloon502 is preloaded over an endoscope 96. The balloon 502 is preferablymade of a compliant material such as silicone or polyurethane, but couldalso be a material such as polyethylene or PET. The wall thickness ofthe balloon is preferably thicker in the middle of the “peanut” to limitthe degree of radial expansion compared to the proximal and distalsections. Alternatively the middle of the balloon is simply blown ormolded to a smaller diameter. The tip of the overtube balloon 502 isfitted with a relatively rigid nipple-shaped dome 504 that allows a snugfit with the tip of the endoscope. The dome 504 may be an integral,thickened portion of the balloon itself, or a separate component thatthe balloon is bonded to. It is conceivable that to aid seating theendoscope 96 in the dome 504 and make later release more reliable, thetip of the endoscope could be secured to the dome with the aid of one ofthe available endoscope channels. For instance, suction from a channelof the endoscope 96 could be applied to hold the dome against theendoscope tip, or a screw or barb or other grasping mechanism could beadvanced through the channel to secure the dome tip to the tip of theendoscope. Also, vacuum may be applied to the balloon 502 using thelumen of the overtube 500, or from a lumen of the endoscope 96, to foldthe balloon 502 down onto the endoscope. The proximal end of theovertube 502 is fitted with appropriate stasis valves to prevent leakageout the proximal end. The balloon 502 and/or the dome 504 should betransparent to allow visualization of tissue structures through theballoon wall.

An optional embodiment (not shown) would be the use of a vent tubealongside the overtube 500 and overtube balloon 520 to allow air in thestomach to vent out of the patient. The tube could be positionedcompletely separate from the overtube or advanced through an optionallumen in the overtube, exiting just proximal to the overtube balloon520. The distal end of the vent tube would be positioned in the stomach20 distal to the overtube balloon 520. The tube is preferably relativelystiff at the proximal end (for push transmission), and floppy at thedistal end so that it is atraumatic and conforms well to the overtubeballoon 520 as the balloon entraps the vent tube against the tissue.While the inner diameter of the vent tube needs to be only on the orderof 0.005″ to vent air, larger inner diameters up to 0.042″ may be usedto speed the aspiration of fluids or allow the passage of a guide wire(for ease in placement). The wall thickness may be 0.003″ to 0.010″,preferably, 0.004″. The wall of the tube may be a solid material, or acomposite of plastic and adhesives and/or stainless steel or nitenolwires or Dacron fibers. The wall may consist of stainless steel,nitenol, or a plastic such as polyurethane, pebax, polyethylene, PET,polyimide, or PVC.

With the endoscope 96 seated in the dome 504 of the balloon 502, theovertube 500 and endoscope 96 are advanced down the esophagus 10 to theregion of the LES 18. As illustrated in FIG. 36, using endoscopyvisualization, and retracting the endoscope as necessary, the balloon ispositioned so that the peanut shape straddles the LES 18.

The balloon is then inflated with a fluid medium (water, saline,contrast, etc.) as illustrated in FIG. 37. Inflation is performedpreferably through the lumen of the overtube, although an availablechannel in the endoscope 96, or lumens in the ablation catheter 32 mayalso be used. The shape of the balloon allows it to conform to thecontours of the esophagus at, and on either side of, the LES. The shapealso helps stabilize the balloon at the LES. The balloon is inflated toa diameter that allows safe dilatation of the folds in the esophagus.The nominal inflated diameter of the proximal section 510 should be 20mm, with a range of 15-30 mm. The distal section 512 can be larger,nominally 40 mm and a range of 15-50 mm. Diameter may be assessed byfluid volume, pressure, endoscopic visualization, or fluoroscopicvisualization. The balloon and the fluid inside form a “couplingchamber” that allows ultrasound energy to be transmitted to the tissuefrom inside the balloon. Addition of contrast to the fluid allowsfluoroscopic visualization of the shape and diameter.

With the balloon inflated, the distal shaft 520 of the ablation catheter32 is advanced out of the endoscope channel 518, as shown in FIGS. 38 aand 38 b. Mounted on the distal shaft 520 is an ultrasound transducer34. The transducer 34 is preferably a cylinder with only one segment ofthe circumference active. Other transducers have been described inprovisional patent application 60/393,339 and are incorporated byreference herein. An external manipulation member (hereafter called pullwire) 530 is positioned on the side of the distal shaft 520 opposite theactive transducer segment. The distal end of the pull wire 530 isattached to a hinge (or weld-joint 528 at the catheter tip, and theproximal end is routed through a lumen orifice 532 in the distalcatheter shaft 520 and out the proximal end of the catheter to anactuator on the hub/handle 38. As the pull wire 530 is tensioned, asoft, kink resistant section 522 of the distal shaft 520 forms a tightbend that allows the transducer to be oriented at the desired angleinside the balloon 502. Compression of the pull wire straightens thedistal shaft 520 and may also bend it in the opposite direction. Theendoscope and/or fluoroscope may be used to determine the properorientation of the transducer relative to the tissue.

With the transducer 34 oriented towards the tissue, cooling flowcirculation is initiated as shown in FIG. 38 b, to prevent heating ofthe mucosa during subsequent energy delivery. Chilled fluid 82 from thepump 80 is preferably routed through a lumen under/behind thetransducer, out the distal orifice 526 and back through the proximal (tothe transducer) orifice 524 to a separate lumen returning to the pump 80or other reservoir. Alternatively, or in addition, chilled fluid may becirculated via the overtube lumen or a lumen in the endoscope.

As shown in FIG. 39, energy from the generator 70 is applied to thetransducer 54, which creates a beam of acoustic energy 35 directedtowards the LES tissue 18. The transducer frequency, power level, andpower duration are chosen to create a lesion 550 a of a desirable size.The catheter 32 may be torqued and the pullwire 530 adjusted to reorientthe transducer to another location around the circumference and/or thelength of the LES region, where energy delivery and lesion creation arerepeated. Ideally, each lesion is formed for about 5-10 mm down theaxial length of the LES at a radial depth of 3-8 mm. As shown in FIG.40, the transducer can also be directed towards the LES 18 from withinthe stomach 12. Also, from the same position, the transducer can beoriented to ablate the gastric cardia 20, just beyond the LES 18.Lesions in the gastric cardia might be more effective in ablating vagalafferent nerve fibers responsible for transient relaxations of the LESand also reduce the compliance of the gastric sling fibers to delaysphincter opening during gastric distension.

FIG. 41 shows another embodiment of the invention where the transducer34 is instead (or in addition to) positioned at the tip of the ablationcatheter to direct energy in the same direction as the axis of thecatheter.

FIG. 42 shows another embodiment where a smaller balloon 502′ is fittedon the tip of the overtube 500 to contain the distal portion of theablation catheter 32. The distal end of the overtube shaft 500 in thiscase is aligned with the distal end of the endoscope 96 and may bedeflected with the endoscope 96. Also as shown in FIG. 42, the pull wiremay be routed through a separate channel of the endoscope (the wirewould need to be back-loaded through the endoscope before it is insertedinto the overtube).

FIG. 43 shows another embodiment where the balloon 502″ is attached tothe distal shaft 520 of the catheter 32, and no overtube is used. Thedistal end of pull wire 530 may be attached to the outside of the shaftproximal to the balloon, or fixed inside the distal shaft.

FIG. 44 shows another embodiment of the overtube 500 where a distalmember 501 extends from the distal opening of the overtube to the distalend of the balloon 502. The distal end of the balloon 502 is bonded tothe distal end of the member 501. The member 501 may have one or morelumens to allow passage of a guide wire 400, and for inflation/deflationof the balloon, and/or circulating cooling fluid within the balloon. Thedistal opening of member 501 may also be used to vent air from thestomach. The endoscope 96 carrying catheter 32 may be advanced throughthe main channel of the overtube 500 as described previously.

FIG. 45 shows another embodiment of the overtube 500 employing the useof a doughnut shaped balloon 502 e attached to the distal end of theovertube. The doughnut shape allows for a central lumen in the balloon.This may be important to vent air from the stomach 12 or allow passageof the endoscope distal to the balloon. The doughnut shape also providesa good reference to the position of the inferior LES when inflated inthe stomach and pulled back against the bottom of the LES.

FIG. 46 illustrates the use of the ablation catheter 32 with theovertube having a doughnut shaped balloon. The distal end of theablation catheter 32 is advanced through the center of the doughnutshaped balloon 502 e. With the transducer 34 aligned in the desiredlocation, the ablation catheter balloon 46 is inflated inside theovertube balloon 502 e. With both the overtube balloon and 502 e and theablation catheter balloon 46 filled with an adequate coupling fluid(i.e., water), the ultrasound energy is able to propagate relativelyundamped until it reaches the tissue of the LES 18 or gastric cardia 20.The fluid inside either or both the overtube balloon 502 e or theablation catheter balloon 46 may be recirculated and chilled to preventoverheating of the transducer 34 or the mucosa. Conceivably, theovertube 500 could have a window opening (not shown) proximal to thedoughnut shaped balloon 502 e. This would allow the balloon 46 of theablation catheter to inflate out of the inner lumen of the overtubeproximal to the overtube balloon 502 e.

FIG. 47 shows another embodiment where the peanut shaped balloon 502 ismounted on the distal ablation catheter shaft 520, and no overtube isused. The ablation catheter may or may not be passed through anendoscope 96. If not passed through an endoscope, an endoscope isadvanced alongside the catheter shaft, or positioned at the desiredlocation and the distance noted before it is removed and the ablationcatheter inserted the same distance. Transducers 34 are mounted on thedistal shaft 520 under to balloon at locations either or both distal andproximal to the LES 18 (the sunken region of the peanut balloon 502).The transducers may be hinged to the side of the shaft and at point 229,and hinged at the other end 528 where a pull wire is attached. The pullwire 530 is routed through the shaft 520 to an actuator on the proximalend of the device. Push and pull of the pull wire 530 may allowswiveling of the transducer to create lesions 551 a-551 d. Thetransducers may also be driven simultaneously while angled to focus atan intersection point within the wall of the LES 18.

Other embodiments focused on a means to change the angle of thetransducer are illustrated in FIGS. 48 a-48 d. In FIG. 48 a, thetransducer is mounted on a shaft member 521, which is advanced out of alumen in the distal shaft 520 of the ablation catheter 32. The shaft 521may have a set curve or be deflectable with an internal pull wire. Itcan be seated in a channel 525 in shaft 520 during advancement andretraction. The transducer 34 can be uni- or multidirectional. In FIG.48 b, the shaft 521 continues distal to the transducer where it is fixedinside shaft 520. Pushing and pulling on the proximal shaft 520 causes aprolapse proximal to the transducer at a soft, kink-resistant point 523.In FIG. 48 c, pull wire 530 is attached to the proximal end of thetransducer at hinge 528. The “pull wire” is pushed forward to increasethe transducer angle, and pulled back to reduce the angle. In FIG. 48 d,the transducer 34 is angulated by inflating a bladder 527 under thetransducer. A floppy tether 529 may be tensioned to fully seat thetransducer 34 and bladder 527 into groove 525 during insertion andremoval.

In another embodiment shown in FIG. 49 a, an endoscope 96 with twoavailable channels is advanced down the esophagus 10 to the region ofthe LES 18. The distal shaft 520 of ablation catheter is advanced out ofone of the available channels of the endoscope 96 to the region of theLES 18 to be treated. Mounted on the distal shaft 520 is an ultrasoundtransducer 34. The transducer 34 is preferably mounted to deliver a beamof acoustic energy in the same direction as the catheter's longitudinalaxis, but could also be designed to deliver energy at other angles tothe axis. The transducer is optionally surrounded distally by a couplingchamber 570, consisting of a rigid or flexible membrane 571 filled withan acoustic coupling medium (e.g., water, saline, gel). The thickness ofthe membrane 571 where the ultrasound energy passes is preferably lessthan one-quarter the wavelength of the ultrasound to preventtransmission loss. One or more temperature sensors 569 may be mounted onthe tip of the membrane 571 in the path of the ultrasound beam 35 tomonitor temperature of the mucosa to prevent overheating.

An occlusion balloon catheter 560 consisting of a catheter shaft 561 andballoon 562 is advanced through another available channel of theendoscope 96 and distal to the LES 18. The balloon 562 is inflated (withair or water via a lumen in the catheter, exiting at port 563 inside theballoon) in the stomach 12 to a diameter larger than the LES opening andthen pulled back against the LES to create a seal. Fluid 565 (e.g.,water, saline) is injected through a lumen in catheter 560, exiting froma port 564 proximal to the balloon, to fill the region of the esophagus10 proximal to the LES 18. This provides a means of ensuring acousticenergy is coupled to the tissue as well as providing a means of coolingthe mucosa to prevent heat damage. The fluid 565 may alternatively oradditionally be infused through a lumen in the endoscope 96. Circulationof the fluid 565 may also be accomplished through multiple lumens inshaft 561 of catheter 560, or endoscope 96.

As shown in FIG. 49 b, an overtube 500 having a balloon 572 bonded tothe distal portion of the overtube shaft may be used to create aproximal seal to contain the fluid 565 infused in the region of the LES18 (the balloon catheter 560 would continue to be used to contain thefluid 565 at the distal portion of the LES 18). As illustrated in FIG.49 b and FIGS. 49 c-e, a stasis valve 573 on the tip of the overtube maybe used to prevent fluid from migrating up the space between theendoscope and overtube, as well as to prevent scraping the mucosa whenthe overtube is moved relative to the endoscope. The valve 573 iscompressible (formed from silicone rubber or polyurethane) toaccommodate a range of endoscope outer diameters. The proximal end ofovertube 500 may be fitted with a similar stasis valve, or o-ring 574which may be manually compressed by turning a threaded nut 575. A sideport luer 576 may be used to flush the lumen of the overtube 500.

Referring back to FIG. 49 a, once the fluid 565 is infused, thetransducer 34 is energized to deliver ultrasound energy 35 to the regionof the LES 18. The energy 35 is delivered for a sufficient time andenergy to create a lesion 575 a in the tissue in the region of the LES18. The process may be repeated multiple times around the circumferenceand/or axis of the LES 18 to create additional lesions, such as 575 b.

In another embodiment shown in FIG. 50, the ablation catheter 32 isconfigured similar to that shown in FIG. 51. The catheter 32 is designedto be preloaded in the endoscope 96 such that an extended portion of theshaft 572 distal to the transducer 34 runs from the distal endoscope,out through the proximal end. This allows manipulation of two shaftelements, 570 and 572, proximal and distal to the transducer,respectively, to change the orientation of the transducer 34. Thetransducer 34 in this configuration is elongated such that its width isapproximately the same as the diameter of the catheter shaft, and thelength is in the range of 3-10 mm. An occlusion balloon catheter 560 isagain positioned distal to the LES, but runs alongside the endoscope 96,not through it. An overtube 500 with balloon 572 may be used in a mannersimilar to that of FIG. 49 b. As described for FIGS. 49 a and 49 b,fluid 565 is infused into the region of the LES 18 and acoustic energy35 is delivered from the transducer 34 into the tissue to form lesionsin various locations such as 576 a and 576 b.

In another embodiment shown in FIG. 51, the distal shaft 520 of ablationcatheter 32 is advanced out of an endoscope 96 in the region of the LES18. In this embodiment, the endoscope only requires one free channel,that dedicated to the ablation catheter 32. The distal shaft 520 of thecatheter 32 is fitted with a transducer 34, mounted along the side ofthe of the catheter shaft. The transducer is surrounded by a membrane580 with features and function similar to that described for FIG. 49 ato aid in coupling of the ultrasound energy to the tissue. The fluid orgel in the membrane may be recirculated to keep the transducer andmucosa cool. Mounted to the opposite side of the shaft 520 from thetransducer 34 is an expandable member 582 designed to force the membrane580 surrounding the transducer 34 securely against the tissue. Theexpandable member 582 is preferably a balloon, but could also consist ofone or more moveable splines designed to bow against the tissue. Aninternal pull wire mechanism (not shown) connected to a proximalactuator could also be employed to aid in deflecting the distal shaft520 against the tissue in the region of the LES 18. Once in positionagainst the tissue, ultrasound energy 35 is delivered from thetransducer 34 to form lesions in various positions in proximity to theLES, such as 577 a and 577 b.

In another embodiment shown in FIG. 52 a and FIG. 52 b, an ablationcatheter 32 is advanced to the region of the LES. Accurate positioningat the LES is accomplished by using markings on the shaft correspondingto previous use of an endoscope, or placing an endoscope alongside theshaft of the ablation catheter. Constructed on the distal end ofcatheter shaft 520 is a tissue chamber 590 designed to accept a portionof the muscle wall in the region of the LES 18. The tissue chamber maymeasure 5-25 mm long and 3-10 mm deep. Constructed proximal to thetissue chamber 590 is a transducer assembly chamber 592. Within chamber592 a transducer assembly 594 is slideable via a piston 596 connected toan actuator on the proximal end of the catheter 32. The transducerassembly 594 consists of a transducer 34 mounted with proximal airbacking and a distal coupling chamber 598 formed by a membrane 599(similar in form and function to that described for FIG. 49). Coolingfluid 600 may be circulated in and out of the chamber 598. Using thepiston 596 the assembly may be pushed down onto the tissue drawn intothe tissue chamber 590. To aid in drawing the tissue into the chamber590 and securing it there, suction from a plurality ports 601 may beemployed. The use on an expandable member 602 (balloon or splines)mounted opposite to the chamber may aid in forcing the catheter into thetissue (and thus the tissue into the chamber 590).

At the distal end of the chamber is an optional chamber 604 that mayalso accept circulated cooling fluid 600 to keep the distal end of themucosa from overheating. Distal to optional chamber 604 is an element606 that can be configured to absorb ultrasound energy not absorbed bythe tissue. This may consist of a highly attenuating material such assilicone or polyurethane rubber. Alternatively, element 606 could beanother transducer 34 that directs energy into the tissue towards thatcoming from the transducer assembly 594 to increase the heating withinthe tissue. An atraumatic tip 608 is attached to the distal tip of thecatheter 32. Once the tissue is pulled into the coupling chamber 590,the transducer assembly 594 pushed against the tissue and infused withcooling fluid 600, ultrasound energy 35 is delivered into the tissue toform a lesion 610.

An alternative embodiment of the device described in FIG. 52 would be tonot require the transducer assembly 594 to be moveable, and therebyeliminate the need for the piston 596. The push force onto the tissuecould be accomplished by designing the membrane 599 to be outwardexpandable. Also, an internal pull wire mechanism (not shown) attachedto the distal tip of the catheter and connected to a proximal actuatorcould also be employed to aid in deflecting the distal shaft 520 againstthe tissue in the region of the LES 18. More specifically, the pull wiremay be used to curl the distal tip 608 (and attached segments 606 and604 under and against the LES tissue.

Other means may be used in addition to or in place of that described forFIG. 52 to draw the tissue into the tissue chamber. FIG. 53 aillustrates grasping mechanisms 620 actuated by pull wires 622 connectedto an actuator at the proximal end of catheter 32. The graspingmechanisms 620 are formed from a metal or hard plastic and containfrictional tread 624 to assist in holding the slippery tissue. They arealso contained within the chamber 590 and hollow in the middle so as tonot interfere with the ultrasound energy. The grasping mechanisms 630illustrated in FIG. 53 b are similar to FIG. 53 a except that they swingout from the catheter shaft to help pull more tissue into the chamber590. Additional tread 632 on the bottom (distal) end of the chamberwould aid in holding the tissue in place. FIG. 53 c shows preformed wire(i.e., stainless steel or nitenol) being advanced out of the cathetershaft to pinch the tissue and help force it into the tissue chamber 590.In FIG. 53 d, two “partial doughnut” balloons are inflated to help pinchand push the tissue into the tissue chamber.

1-26. (canceled)
 27. A method of intraluminal ablation of nerve tissuesurrounding a bodily lumen of a subject, comprising: delivering anablation device within a bodily lumen of a subject, said ablation devicecomprising a catheter and at least one energy delivery elementpositioned along a distal end of the catheter, said at least one energydelivery element comprising at least one ultrasound transducer, whereinthe catheter comprises at least one fluid passage and a balloonpositioned along a distal end of the catheter, said balloon configuredto surround the at least one energy delivery element, said at least onefluid passage being in fluid communication with said balloon; advancingthe ablation device within the bodily lumen to position the at least oneenergy delivery element adjacent target nerve tissue of the subject; atleast partially inflating the balloon by delivering a cooling fluidthrough the at least one fluid passage of the catheter; circulating acooling fluid through an interior of the balloon via the at least onefluid passage of the catheter to remove heat away from the at least oneenergy delivery element; and activating the at least one energy deliveryelement to deliver energy radially outwardly from said at least oneenergy delivery element through the balloon and toward a wall of thebodily lumen, wherein the at least one energy delivery element isactivated so that sufficient energy is delivered to at least partiallyablate nerve tissue adjacent the wall of the bodily lumen; whereincooling fluid is circulated through the interior of the balloon duringat least a portion of the time when the at least one energy deliveryelement is activated; and wherein circulating cooling fluid through aninterior of the balloon reduces the likelihood of heating a lining ofthe bodily lumen to the point of irreversible damage.
 28. The method ofclaim 27, wherein at least partially inflating the balloon comprisesproviding sufficient fluid within an interior of said balloon so thatsaid balloon at least partially engages the wall of the bodily lumen.29. The method of claim 27, wherein energizing the at least one energydelivery element raises a temperature of a targeted anatomical tissue byapproximately 55° C. to 95° C.
 30. The method of claim 27, whereinenergizing the at least one energy delivery element raises a temperatureof a targeted anatomical tissue by approximately 60° C. to 80° C. 31.The method of claim 27, wherein the balloon comprises at least onecomplaint material.
 32. The method of claim 27, wherein the ballooncomprises at least one non-complaint material.
 33. The method of claim27, wherein the at least one ultrasonic transducer is configured to emitunfocused acoustic energy.
 34. A method of intraluminal ablation ofnerve tissue surrounding a bodily lumen of a subject, comprising:inserting an ablation device within a bodily lumen of a subject, saidablation device comprising a catheter and an energy delivery elementlocated along a distal end of the catheter, wherein the cathetercomprises a balloon, said balloon generally surrounding the energydelivery element; advancing the ablation device within the bodily lumenin order to position the energy delivery element near a targetanatomical location of the subject; at least partially inflating theballoon by delivering a fluid through at least one fluid passage of thecatheter and into an interior of said balloon; activating the energydelivery element to emit energy outwardly from said energy deliveryelement toward and through a wall of the bodily lumen so as to ablatenerve tissue positioned adjacent the wall of the bodily lumen; whereindelivering a fluid to the interior of the balloon reduces the likelihoodof heating an inner lining of the bodily lumen to the point ofirreversible damage; and wherein delivering a fluid to the interior ofthe balloon to at least partially inflate the balloon generally radiallycenters the energy delivery element within the bodily lumen.
 35. Themethod of claim 34, further comprising circulating a fluid through aninterior of the balloon, at least for a portion of a time when theenergy delivery element is activated, via the at least one fluid passageto remove additional heat away from the energy delivery element.
 36. Themethod of claim 34, wherein at least partially inflating the ballooncomprises providing sufficient fluid within the interior of said balloonso that said balloon at least partially contacts the wall of the bodilylumen.
 37. The method of claim 34, wherein the energy delivery elementcomprises at least one ultrasonic transducer.
 38. The method of claim34, wherein the energy delivery element comprises at least oneradiofrequency (RF) electrode.
 39. The method of claim 34, wherein theenergy delivery element comprises at least one of a microwave emitterand a laser emitter.
 40. The method of claim 34, wherein activating theenergy delivery element raises a temperature of a targeted anatomicaltissue by approximately 55° C. to 95° C.
 41. A method of intraluminalablation of nerve tissue surrounding a bodily lumen of a subject,comprising: inserting an ablation device within a bodily lumen of asubject, wherein the ablation device comprises a catheter and at leastone energy delivery element located near a distal end of the catheter,said catheter comprising at least one fluid passage and a balloongenerally surrounding the at least one energy delivery element, whereinthe at least one fluid passage is in fluid communication with aninterior of the balloon; advancing the ablation device within the bodilylumen in order to position the energy delivery element near a targetanatomical location of the subject; at least partially inflating theballoon by circulating a cooling fluid through the least one fluidpassage of the catheter and into the interior of said balloon;activating the energy delivery element to deliver sufficient energyoutwardly from said energy delivery element toward a wall of the bodilylumen to ablate nerve tissue positioned adjacent the wall of the bodilylumen; wherein cooling fluid is circulated through the interior of theballoon during at least a portion of the time when the energy deliveryelement is activated to transfer heat away from the energy deliveryelement; and wherein delivering a cooling fluid to the interior of theballoon reduces the likelihood of heating an inner lining of the bodilylumen to the point of irreversible damage.
 42. The method of claim 41,wherein the at least one energy delivery element comprises at least oneultrasonic transducer.
 43. The method of claim 41, wherein the at leastone energy delivery element comprises at least one radiofrequency (RF)electrode.
 44. The method of claim 41, wherein the at least one energydelivery element comprises at least one of a microwave emitter and alaser emitter.
 45. The method of claim 41, wherein at least partiallyinflating the balloon comprises providing sufficient cooling fluidwithin the interior of said balloon so that said balloon at leastpartially contacts the wall of the bodily lumen.
 46. The method of claim41, wherein circulating a cooling fluid within the interior of theballoon comprises circulating said cooling fluid through at least twoseparate fluid passages of the catheter.